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Biomedical subjects

S Hunt

Publications and source records attributed to S Hunt.

At least 19 recordsLinked to original sources
PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗
PubMed2002

The quality of life in men after radical cystectomy with a continent cutaneous diversion or orthotopic bladder substitution: is there a difference?

OBJECTIVE: To compare the quality of life (QoL) in men after radical cystectomy who had either a continent cutaneous diversion or orthotopic bladder substitution. PATIENTS AND METHODS: Eighty men with at least 6 months of follow-up and with no signs of recurrent disease after radical cystectomy for bladder carcinoma, and who had either a continent cutaneous diversion or orthotopic bladder substitution, were sent two types of questionnaire, the Functional Assessment of Cancer Therapy-Bladder Cancer (FACT-Bl) and the Hospital Anxiety and Depression Scale (HADS), to determine their QoL. RESULTS: The FACT-Bl and HADS questionnaires were returned by 90% and 71% of the patients, respectively (P < 0.05). In the replies to the generic version of FACT-Bl there were no differences between the groups in any domain, the scores being high in all. In questions covering intestinal, urinary and sexual items, patients with continent diversion had less trouble controlling urine (P < 0.0001), had to empty less often (P < 0.001), and had fewer symptoms when emptying (P < 0.05). Patients with neobladders had a better appreciation of appearance and better preserved erectile function (both P < 0.05). In the answers to the HADS, the mean scores were low (within the normal ranges) and did not differ between the groups. CONCLUSION: Using two instruments tested for validity and reliability, there were no differences between patients with continent diversion and those with orthotopic substitution.

Aged↗
PubMed2001

Impact of cytomegalovirus hyperimmune globulin on outcome after cardiothoracic transplantation: a comparative study of combined prophylaxis with CMV hyperimmune globulin plus ganciclovir versus ganciclovir alone.

BACKGROUND: Cytomegalovirus (CMV) disease was previously shown to be unaltered by a 28-day course of ganciclovir compared with placebo in seronegative recipients of hearts from seropositive donors (D+/R-). This study tests the hypothesis that a combination of ganciclovir plus CMV hyperimmune globulin (CMVIG) is more effective than ganciclovir alone for preventing acute CMV illness and its long-term sequelae. METHODS: The study population receiving CMVIG (n=80) included 27 heart transplant recipients (D+/R-) and 53 heart-lung and lung transplant recipients (R+ and/or D+). Each group was matched with historical controls who underwent transplantation within the preceding 2-3 years. Outcome measures compared were as follows: 3-year incidence of CMV disease; fungal infection; acute rejection; survival; rates and severity of transplant coronary artery disease (in heart patients) defined by intimal thickness (ultrasound) and coronary artery stenosis (angiographic); and incidence and death from obliterative bronchiolitis defined by pathological criteria on endobronchial biopsy specimens (in heart-lung/lung patients). RESULTS: Patients treated with CMVIG had a higher disease-free incidence of CMV, lower rejection incidence, and higher survival rate compared with the patients treated with ganciclovir alone. The coronary artery intimal thickness and the prevalence of intimal thickening were lower in the patients receiving CMVIG. Heart-lung and lung transplant patients treated with CMVIG had lower incidences of obliterative bronchiolitis and death from obliterative bronchiolitis and longer survival compared with the patients treated with ganciclovir alone. CONCLUSIONS: CMVIG plus ganciclovir seems to be more effective that ganciclovir alone for preventing the sequelae of CMV infection. A prospective randomized study is required to confirm these observations.

Adult↗
PubMed2001

Replication dynamics of the yeast genome.

Oligonucleotide microarrays were used to map the detailed topography of chromosome replication in the budding yeast Saccharomyces cerevisiae. The times of replication of thousands of sites across the genome were determined by hybridizing replicated and unreplicated DNAs, isolated at different times in S phase, to the microarrays. Origin activations take place continuously throughout S phase but with most firings near mid-S phase. Rates of replication fork movement vary greatly from region to region in the genome. The two ends of each of the 16 chromosomes are highly correlated in their times of replication. This microarray approach is readily applicable to other organisms, including humans.

Algorithms↗
PubMed2001

Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center.

A total of 1073 infectious episodes (IEs) that occurred in 620 consecutive heart transplantation patients at Stanford Medical Center between 16 December 1980 and 30 June 1996 were reviewed. Infectious complications were a major cause of morbidity and mortality, second only to rejection as the cause of early deaths and the most common cause of late deaths. Of the IEs, 468 (43.6%) were caused by bacteria, 447 (41.7%) by viruses, 109 (10.2%) by fungi, 43 (4.0%) by Pneumocystis carinii, and 6 (0.6%) by protozoa. The largest number of IEs occurred in the lungs (301 [28.1%]). A significant reduction in the incidence of IEs and a delay in presentation after transplantation were observed; these were most likely related to the introduction of new chemoprophylactic regimens during the study period and prevention of significant disease caused by cytomegalovirus.

Adult↗
PubMed2001

Metabolic abnormalities characteristic of dysmetabolic syndrome predict the development of transplant coronary artery disease: a prospective study.

BACKGROUND: This study examines the hypothesis that metabolic abnormalities of dysmetabolic syndrome are risk factors for transplant coronary artery disease (TxCAD). METHODS AND RESULTS: Sixty-six patients without overt diabetes, 2 to 4 years after surgery, underwent intracoronary ultrasound (ICUS), measurement of plasma glucose and insulin after oral glucose (75 g), and fasting lipid and lipoproteins. TxCAD incidence by angiography or autopsy was prospectively determined during subsequent follow-up (8 years). Coronary artery intimal thickness (IT) and subsequent outcomes were compared in patients stratified as having "high" versus "low" plasma glucose (>8.9 mmol/L) and insulin (>760 pmol/L) 2 hours after glucose challenge; and "abnormal" versus "normal" fasting lipid and lipoprotein concentrations as defined by the National Cholesterol Education PROGRAM: Patients with high glucose or insulin concentrations had greater IT: 0.38+/-0.05 versus 0.22+/-0.02 mm, P</=0.05, and 0.39+/-0.05 versus 0.20+/-0.02 mm, P</=0.01, respectively. Freedom from TxCAD was 56+/-11% versus 81+/-6% (P<0.01) in patients with high versus low glucose and 57+/-10% versus 82+/-7% (P<0.05) in patients with high versus low insulin. Actuarial survival was 60+/-12% versus 92+/-5% (P<0.005) in patients with high versus low glucose and 72+/-9% versus 88+/-6% (P<0.05) in patients with high versus low insulin. Triglycerides and VLDL were higher and HDL was lower in patients with IT >0.3 mm than with IT </=0.3 mm. TxCAD incidence was higher in patients with high plasma TG and VLDL and low HDL. CONCLUSIONS: These data suggest that insulin resistance plays a role in TXCAD:

Adult↗
PubMed2001

A SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence.

The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR-RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]

Base Composition↗
PubMed2001

Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease.

BACKGROUND AND AIM: The immunosuppressive properties of 6-mercaptopurine and its parent compound azathioprine are mediated by their intracellular metabolism into active 6-thioguanine (6-TG) metabolites. Measurement of erythrocyte 6-TG metabolite levels has been proposed as a useful clinical tool for assessing treatment efficacy in patients with inflammatory bowel disease (IBD). AIM: The purpose of the study was to establish a therapeutic index of treatment efficacy based on measurement of erythrocyte 6-TG metabolite levels, and apply it clinically to guide therapy. METHODS: Heparinised blood was obtained from 82 adult patients with IBD on long term (more than three months) antimetabolite therapy (63 Crohn's disease; 19 ulcerative colitis). Erythrocyte 6-TG metabolite levels were measured using reverse phase high performance chromatography, and correlated with treatment efficacy. In 22 patients with refractory Crohn's disease despite long term azathioprine therapy, their dosage was increased by 25 mg/day at eight week intervals as needed. Serial erythrocyte 6-TG metabolite levels were measured at each clinic visit and correlated with treatment efficacy. RESULTS: Clinical remission, as defined by a low disease index score in patients weaned off or on a low alternate day dose (<20 mg on alternate days) of corticosteroid, was achieved in 68% of patients on long term antimetabolite therapy. Treatment efficacy correlated with erythrocyte 6-TG levels greater than 250 pmol/8x10(8) red blood cells in patients with colonic and fistulising Crohn's disease (p<0.01) but not in patients with ileocolonic disease. Eighteen of 22 patients with incompletely responsive Crohn's disease achieved disease remission by optimising their dose of azathioprine therapy. Median (range) erythrocyte 6-TG metabolite levels increased from 194 (67-688) to 303 (67-737) pmol/8x10(8) red blood cells (p<0.05). Clinical response associated well with a reduction in corticosteroid requirements. Mean (SEM) white blood cell count decreased from 8.6 (0.9) to 6.9 (0.6) x10(3)/microl with adjustment in azathioprine dosage. No patient incurred azathioprine induced leucopenia. CONCLUSION: Measurement of erythrocyte 6-TG metabolite levels is helpful in determining the adequacy of azathioprine dosage and can be used to optimise the dose of antimetabolite therapy to achieve an improved clinical response without inducing leucopenia. Patients who are clinically refractory to azathioprine therapy despite achieving high erythrocyte 6-TG levels (>250) should be considered for adjunct or alternative forms of immunosuppressive therapy or surgery.

Adolescent↗
PubMed2001

Is the ultraviolet waveband a special communication channel in avian mate choice?

There is growing evidence that ultraviolet (UV) wavelengths play an important role in avian mate choice. One of the first experiments to support this idea showed that female zebra finches (Taeniopygia guttata) prefer UV-reflecting males to males whose ultraviolet reflection has been removed. The effect was very strong despite little or no UV reflection from several plumage areas. However, it is not clear how the importance of the UV waveband compares to other regions of the bird-visible spectrum. We tested whether the response of female zebra finches to the removal of male UV reflection is greater than to the removal of other wavebands. We presented females with a choice of males whose appearance was manipulated using coloured filters. The filters removed single blocks of the avian visible spectrum corresponding closely to the spectral sensitivities of each of the zebra finch's single cone classes. This resulted in males that effectively had no UV (UV-), no short-wave (SW-), no medium-wave (MW-) or no long-wave (LW-) plumage reflection. Females preferred UV- and SW- males. LW- and MW- males were least preferred, suggesting that female zebra finches show the greatest response to the removal of longer wavelengths. Quantal catches of the single cone types viewing body areas of the male zebra finch are presented for each treatment. Our study suggests it is important to consider the role of the UV waveband in avian mate choice in conjunction with the rest of the avian visible spectrum.

Animal Communication↗
PubMed2001

Counseling female athletes: application of the stages of change model to avoid disordered eating, amenorrhea, and osteoporosis.

Research indicates that female athletes from all sports are at risk for developing disordered eating. amenorrhea, and resulting complications. These disorders, termed the female athlete triad by the American College of Sports Medicine, may lead to significant morbidity and mortality as well as medical and psychological problems. When female athletes feel pressured to fit a specific physical image, they may develop distorted body images and show disordered eating patterns. Menstrual dysfunction and premature osteoporosis may result from inadequate nutrition combined with excessive athletic training. Health professionals play important roles in prevention and treatment of these problematic behaviors. This paper examined the stages of the change behavior model and its use in addictive behaviors and provides theoretical applications of this model to reducing harmful behaviors in female athletes.

Adult↗
PubMed2001

Technology evaluation: HspE7, StressGen Biotechnologies Corp.

StressGen is developing HspE7 (SGN-00101) as a potential therapy for human papillomavirus (HPV)-associated conditions. It is a recombinant fusion protein comprising the HPV E7 antigen and the heat shock protein, hsp65, from Mycobacterium bovis. By November 2000, it was in phase III trials for HPV-related anal dysplasia [405228]. Under an aggrement formed in November 1999, the US National Cancer Institute (NCI) is carrying out clinical trials with StressGen in diseases caused by HPV [347155].

Bacterial Proteins↗
PubMed2001

Technology evaluation: IMC-1C11, ImClone Systems.

ImClone is developing IMC-IC11, an anti-angiogenesis chimeric monoclonal antibody specific vascular endothelial growth factor receptor 2 (VEGFR-2, also known Flk-1 in mice), for the potential treatment of cancer [156625]; it in phase I trials for the treatment of colorectal carcinoma [379143]. The related antibody DC-101 provided proof-of-principle that an anti-VEGF receptor antibody could strongly inhibit tumor growth and even cause tumor regression with the glioblastoma tumor cell line, GBM18 [388236]. In May 1998, the company was granted US-05747651 by the USPTO, covering antibodies against the extracellular portion of the FLK-1/KDR receptor [284054].

Angiogenesis Inhibitors↗
PubMed2001

Technology evaluation: anticancer gene therapy, MediGene.

MediGene is developing recombinant adeno-associated virus (rAAV) vectors for the potential treatment of cancer, and in particular, melanoma and ovarian cancer [304021]. In June 2001, MediGene and its collaborator Aventis Pharma announced the start of a phase I/II trial for a vaccine against malignant melanoma [413513]. The therapy works by boosting the patient's immune response. Autologous or allogeneic tumor cells are transduced with recombinant adeno-associated virus (rAAV) vectors, which express immunomodulators, such as cytokines, and are then expanded in vitro. Following irradiation, these gene-modified cells are reintroduced to the host, leading to a specific antitumor response against the patient's own tumor cells [221820].

Animals↗
PubMed2001

Technology evaluation: MetXia-P450, Oxford Biomedica.

Oxford BioMedica is developing gene therapies for treating various forms of cancer. The therapies comprise the transfer of several anticancer genes at a time using a recombinant retrovirus approach based on the company's proprietary LTR Deleted Vector and Accelerated Vector Evolution technologies [238147]. MetXia-P450 is a gene therapy construct containing the cytochrome P450 gene CYP2B6, and is designed to be injected directly into tumors to convert them into 'drug factories'. This is achieved because CYP2B6 converts the inactive produg form cyclophosphamide into the active cytotoxic drug. MetXia-P450 is in phase I/II trials for breast cancer [339582].

Aryl Hydrocarbon Hydroxylases↗